Some medical practitioners believe that separating platelet-rich plasma from a patient's whole blood immediately prior to surgery and then sequestering it until the surgery is over, thereby avoiding trauma to the platelets, has therapeutic benefits. Although the benefits are not well understood, some proponents of plasma sequestration believe that it minimizes the potential for platelet activation and/or the harmful effects associated therewith. Plasma sequestration may be particularly useful for cardiovascular procedures involving blood oxygenation by minimizing the potential for damage to platelets and clotting factors. In plasma sequestration, whole blood is processed by withdrawing it from the patient, separating the plasma from the whole blood by centrifugation, and collecting the plasma for later reinfusion. The patient thus receives a supply of autologous plasma, including platelets and clotting factors, following surgery. Some proponents of plasma sequestration also believe that this procedure helps to reduce blood loss following surgery and/or enhances the rate of wound healing by supplying a source of post-operative platelets.
In addition to these potential therapeutic benefits, plasma sequestration may also reduce or eliminate the need for homologous blood. Procedures which reduce the need for homologous blood products are currently of particular interest due to the growing concern over the possibility of disease transmission via transfusions of homologous blood products. The use of autologous blood products eliminates the risk of exposure to transfusion-transmitted disease and reduces the risk of febrile/allergic transfusion reactions. The use of autologous blood products also eliminates the need for compatibility testing.
Known methods of plasma sequestration generally comprise the following steps: (1) collecting and anticoagulating the patient's whole blood; (2) processing the blood to separate plasma and red blood cells; (3) returning the red blood cells immediately after processing; and (4) returning the plasma during or immediately following surgery. The blood collecting step can occur during surgery (intraoperative) or before surgery commences (perioperative). In the separation step, the blood is pumped into a spinning centrifuge bowl. Red blood cells, being the most dense of the components, are packed within the centrifuge bowl at the most radially outward location, whereas the plasma forms a layer more radially inward relative to the packed red cell layer. Although platelets can be found throughout the plasma and red cell layers, they tend to concentrate in a relatively thin, whitish layer, called the buffy coat, located at the interface between the plasma and red cell layers. The speed at which blood is pumped into the bowl, the centrifuge speed, the centrifuge bowl design, and the interference of red cells as platelets migrate through them all affect the separation of blood components.
Various automated and semi-automated blood processing systems have been designed to optimize blood component separation efficiency while minimizing operator involvement. Most of these systems are designed for blood component separation in general, not specifically for plasma sequestration. Many of these systems use an optical sensing device to partially or fully automate component separation. U.S. Pat. No. 4,151,844 (Cullis et al.), for example, discloses a centrifugation pheresis system comprising an optical sensing device monitoring the buffy coat outlet tubing. The optical sensing device monitors the composition or optical density of the buffy coat leaving the separation chamber; low density indicates dilution with plasma, high density indicates red cell contamination. When the density of the buffy coat increases or decreases beyond a predetermined range, defining a desired buffy coat composition, the control circuit adjusts the rates of withdrawal of the red blood cells and the plasma accordingly.
T. Simon et al. (1992) "Storage and Transfusion of Platelets Collected by an Automated Two-Stage Apheresis Procedure," Transfusion 32:624-628 discloses an automated plasmapheresis system wherein a detector monitors the optical characteristics of the plasma in the outlet tubing. The control circuit then adjusts the rate of plasma flow and the centrifuge speed to increase platelet concentration (higher optical density) with minimal red cell contamination. If red cell contamination exceeds predetermined levels, the system diverts that plasma back to the centrifuge for repeat processing. Blood processing continues until the desired weight of plasma is produced.
U.S. Pat. No. 4,608,178 (Johansson et al.) and C. F. Hogman (1988) "The Bottom and Top System: A New Technique for Blood Component Preparation and Storage," Vox Sang 55:211-217, disclose a "top/bottom" bag in which the upper plasa and the lower red cell portions can be simultaneously withdrawn from the bag without removing the intermediate buffy coat layer. The "top/bottom" bag includes a sensor to monitor the position of the buffy coat layer while the plasma is withdrawn from the top of the bag and the red cells are withdrawn from the bottom.
Other automated and semi-automated pheresis systems which utilize optical sensing devices include U.S. Pat. No. 5,102,407 (Carmen et al.); U.S. Pat. No. 5,154,716 (Bauman et al.); U.S. Pat. No. 4,498,983 (Bilstad et al.); WO 88/05691 (Brown et al.); and Strauss et al. (1987) "Comparison of Autosurge versus Surge Protocols for Discontinuous-Flow Centrifugation Plateletpheresis," Transfusion 27:499-501. U.S. Pat. Nos. 5,102,407 and 5,154,716 disclose blood fractionation systems which can be semi-automated with sensors, located within the fluid outlet ports, to monitor and control the withdrawal of the separated constituents. U.S. Pat. No. 4,498,983 discloses an automated blood processing system comprising an optical sensor positioned within the separation chamber. The sensor monitors the level of packed red cells and, when the level of packed red cells within the chamber reaches a predetermined level, initiates reinfusion of the processed blood. WO 88/05691 discloses a pheresis system comprising an interface sensor for monitoring the location of the interface between the separated plasma and packed red blood cells during centrifugation. Strauss et al. (1987) discloses a plateletpheresis system using optical sensors which reportedly "monitor all aspects of the collection cycle and [which] automatically adjust the machine settings and the speed of plasma recirculation." AuBuchon et al. ("Optimization of Parameters for Maximization of Plateletpheresis and Lymphocytapheresis Yields on the Haemonetics Model V50" (1986) J. Clin. Apheresis 3:103-108) discloses an automated apheresis system wherein the volume offset setting is adjusted to compensate for the donor's hematocrit.
Blood processing systems which rely on features other than optical sensing devices for automation (or partial automation) include U.S. Pat. No. 4,417,884 (Schoendorfer et al.); U.S. Pat. No. 4,402,680 (Schoendorfer); U.S. Pat. No. 4,968,295 (Neumann); and WO 90/01970 (Ford). U.S. Pat. No. 4,417,884 discloses a centrifuge blood processing system under the control of a timing mechanism, wherein the timing mechanism depends on the speed and duration of the centrifugal force. U.S. Pat. No. 4,402,680 discloses a system for separating blood components using a valve means, such as a stopper ball, which seals the outlet port based upon the specific gravity difference between the blood components. U.S. Pat. No. 4,968,295 discloses a blood fractionation system in which the centrifuge speed responds to the input blood flow rate, thus maintaining constant volume ratios of whole blood and blood fractions.
WO 90/01970 discloses an automated plasmapheresis system wherein the collection and reinfusion cycles depend on the volumes of collected components. Specifically, the collection cycle terminates and the reinfusion cycle begins when a predetermined volume of packed cells has been stored in a reservoir. Once the red cell reservoir is emptied, the system alternates between the collection and reinfusion cycles until a predetermined volume of plasma has been collected, at which time the systems stops.
Although many of the existing automated blood processing systems purport to provide improved separation efficiency and product uniformity, none provide a means for customizing the process to produce a desired product composition. More specifically, none of these separation systems permit customized separation to produce a specific product composition while accommodating multiple system parameters. Most existing systems merely stop the process at some preselected point, for example, when the plasma in the centrifuge outlet tubing exceeds a predetermined optical density or turns a certain color. In fact, the latter method is the only means for assessing completion of the fill cycle in existing plasma sequestration systems, which currently are not automated. Monitoring the outlet tubing to determine when to stop the fill cycle, however, results in an uncertain end point and an inconsistent product. A need therefore exists for a blood processing system, and more particularly a plasma sequestration system, which permits customized separations and which automatically determines when to stop the fill cycle and start the empty cycle.